The objectives of this proposal are to study factors involved in regulation of the rates of degradation of cellular enzymes. Two approaches will be used; (1) Testing the effects of ligands on susceptibility of enzymes to proteolytic attack. The effects of substrates, products, coenzymes, and allosteric effectors on susceptibility of selected enzymes to inactivation by various cellular proteases and to trypsin will be studied. (2) Testing for quantitative and qualitative changes in proteases during periods of enzymic transition. Rats will be subjected to a regimen of starvation and refeeding, changes that have marked effects on levels and rates of degradation of glycolytic, gluconeogenic, and lipogenic enzymes. Specific activities of liver proteases will be tested, as will the ability of subcellular fractions to inactivate various enzymes. Individual proteases will be separated by ion exchange and gel chromatography, and tested for their ability to inactivate various enzymes.